Plasmodium vivax takes a great toll on humanity as a widespread and devastating pathogen, and a vaccine would be a blessing. Although technologies are advancing to make such discoveries possible, there are currently no surrogate markers of protection yet identified for P. vivax vaccines. The lack of robust in vitro cultures for P. vivax is a fact, but not the main hindrance. Model systems to study P. vivax and test vaccine candidates in preclinical trials have been available. However, investment to use these models and develop P. vivax vaccines has been minimal. In stark comparison with Plasmodium falciparum research, with much more investment, only three P. vivax vaccine candidate antigens have gained any traction for clinical trials. Increased financial support in light of new enabling and high-throughput technologies will predictably prove fruitful. A greatly improved understanding of natural and vaccine-induced immune responses is critical and possible today, as well as investigations of novel delivery systems that strategically target particular desired potent outcomes. Modern systems biology approaches in particular have the potential to reveal new vaccine candidates and host–pathogen interactions that may give insights for novel vaccine design and delivery. The identification of surrogate markers of protection for P. vivax could therefore be imminent.